Dataset Information

Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.

ABSTRACT: GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative) among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03-1.39), 1.24 (1.07-1.43), and 1.17 (1.01-1.36), respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent manner (P trend < 0.01); however, only rs2981579 was associated with Luminal-B, and none were linked to ER-&PR- subtypes (ER-&PR-&HER2+ and triple negative). Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B), but not with ER-&PR- subtypes. Our results suggest that associations of FGFR2 SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.

SUBMITTER: Liang H

PROVIDER: S-EPMC4573424 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.

Liang Huiying H Yang Xuexi X Chen Lujia L Li Hong H Zhu Anna A Sun Minying M Wang Haitao H Li Ming M

BioMed research international 20150903

GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative) among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymo ...[more]

PMID: 26421298

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Project description:BackgroundThe discovery of breast cancer subtypes and subsequent development of treatments aimed at them has allowed for a great reduction in the mortality of breast cancer. But despite this progress, tumors with similar characteristics that belong to the same subtype continue to respond differently to the same treatment. Five subtypes of breast cancer, namely intrinsic subtypes, have been characterized to date based on their gene expression profiles. Among other characteristics, subtypes vary in their degree of intra-subtype heterogeneity. It is not clear, however, whether this heterogeneity is shared across all tumor traits. It is also unclear whether individual traits can be highly heterogeneous among a majority of homogeneous traits.ResultsWe employ network theory to uncover gene modules and accordingly consider them as tumor traits, which capture shared biological processes among the subtypes. We then use the β-diversity metric from ecology to quantify the heterogeneity in these gene modules. In doing so, we show that breast cancer heterogeneity is contained in gene modules and that this modular heterogeneity increases monotonically across the subtypes. We identify a core of two modules that are shared among all subtypes which contain nucleosome assembly and mammary morphogenesis genes, and a number of modules that are specific to subtypes. This modular heterogeneity, which increases with global heterogeneity, relates to tumor aggressiveness. Indeed, we observe that Luminal A, the most treatable of subtypes, has the lowest modular heterogeneity whereas the Basal-like subtype, which is among the hardest to treat, has the highest. Furthermore, our analysis shows that a higher degree of global heterogeneity does not imply higher heterogeneity for all modules, as Luminal B shows the highest heterogeneity for core modules.ConclusionsOverall, modular heterogeneity provides a framework with which to dissect cancer heterogeneity and better understand its underpinnings, thereby ultimately advancing our knowledge towards a more effective personalized cancer therapy.

Dataset Information

Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.

Publications

Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.

Similar Datasets

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